Research in this group examines the functional organization of the basal ganglia, a major neural system through which the cerebral cortex affects behavior. The major component of the basal ganglia, the striatum, receives inputs from most of the cortex. The ultimate goal of our research is to understand how the striatum processes cortical information. Three major lines of research are followed: 1) Detailed neuroanatomical mapping of basal ganglia connections, 2) characterization of striatal output neurons in terms of their connections, and expression of repetoires of neurotransmitter receptor subtypes, signal transduction systems, and neurotransmitters/peptides, and 3) pharmacologic manipulations of dopaminergic, cholinergic and peptidergic systems to determine the functional organization of the striatum using quantitative in situ hybridization histochemistry. Neuroanatomical studies reveal a hierarchical organization of functional compartments within the striatum that reflect parallel processing of cortical information. These parallel pathways are revealed by their connections and neurochemical phenotypes. For example, the two major output systems of the striatum, the striatonigral and striatopallidal pathways respectively express D1 and D2 dopamine receptor subtypes. In normal behavior there is a delicate balance between these two pathways, which regulate excitatory and inhibitory activity of the major output systems of the basal ganglia. In Parkinson's disease, the normal balance is disrupted and the striatopallidal pathway appears to become overactive. Studies from this research group have provided insights into the cellular and molecular mechanisms underlying basal ganglia dysfunction, and provided potential new strategies for pharmacologic treatment of Parkinson's disease.